Cytomegalovirus infection modulates the phenotype and functional profile of the T-cell immune response to mycobacterial antigens in older life

Exp Gerontol. 2014 Jun;54(100):94-100. doi: 10.1016/j.exger.2013.12.007. Epub 2013 Dec 25.


Infection with Cytomegalovirus is associated with accelerated immunosenescence. Expansions of CMV-specific T cell responses have previously been demonstrated to affect the ability of T cells to respond to other infections. Most people above 60years of age display M. tuberculosis-specific immunity because of vaccination, exposure, or both. T-cell responses can be assessed by measuring intracellular IFN-γ in vitro after tuberculin stimulation. Here we investigated tuberculin-specific CD4 T-cell responses in independently living healthy older people in the South of England using flow-cytometry. Individuals were investigated for tuberculin and CMV-specific T-cell immunity using in vitro antigen stimulation followed by intracellular staining for IFN-γ, TNF-α, IL2, as well as degranulation and CD154 upregulation. We also examined a control group of younger individuals (20-35years of age). There was no significant difference between older and young people in regards to tuberculin responsiveness of CD4 T-cells; however, older people seemed to show more outliers. Increased responsiveness to tuberculin was significantly correlated to CMV responsiveness but not age. In older donors, the memory phenotype of tuberculin-induced T-cells was significantly skewed towards a more terminal differentiation phenotype in CMV-infected compared to uninfected individuals and the degree of skewing correlated quantitatively with the size of the CMV-specific CD4 T-cell response. This is a fundamental advance over previous reports of changes of the tuberculin-specific CD4 T-cell response with CMV serostatus. Our results show that how the immune system responds to CMV has a fundamental impact on the phenotype and function of the immune response to mycobacterial antigens in older life.

Keywords: Cytomegalovirus; Flow-cytometry; Immunosenescence; T-cell response; Tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Bacterial / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Case-Control Studies
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology*
  • Humans
  • Immunity, Cellular / physiology*
  • Indicators and Reagents / pharmacology
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Mycobacterium tuberculosis / immunology
  • Phenotype
  • Tuberculin / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation


  • Antigens, Bacterial
  • Indicators and Reagents
  • Interleukin-2
  • Tuberculin
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma